Subclinical Anemia Research Articles

Necessity of Implementing Ferritin Testing for Regular Blood Donors – A Cross-sectional Analysis of Serum Ferritin Levels in Individuals Donating Blood at Various Frequencies in a Year at a Regional Blood Transfusion Center

Background and Objectives: The virtuous act of blood donations should be encouraged and promoted by all means while safeguarding the well-being of the donor. If regular blood donations lead to iron store depletion in any individual, it may be identified and preventive measures should be taken. The current practice of hemoglobin (Hb) testing alone before donation may not detect the depletion of iron stores. Yet, a policy to introduce tests for iron stores and iron supplementation in regular donors requires extensive research in this area because of the cost and feasibility concerns. The objectives were to study the prevalence of subclinical anemia among voluntary blood donors using serum ferritin levels attending the blood transfusion center and to compare the average Hb and serum ferritin levels of donors across different age groups, gender, and donation frequencies. Methods: A cross-sectional study was done on 300 consecutively enrolled voluntary whole-blood donors (December 2018–November 2019) who fulfilled eligibility criteria. Donors were further divided into four groups, depending on their number of donations. Their samples were tested for Hb and serum ferritin to check for reduced body iron stores. The data obtained were analyzed using SPSS version 23. Results: A total of 300 regular voluntary donors were included in the study. 57.7% of donors were in the age group of 20–29 years, of which 83.33% were males. The total prevalence of subclinical anemia was 16%, in whom 54.2% were males and 45.8% were females. Out of the total female donors in our study (50), 44% suffered from subclinical anemia. Out of the total male donors in the study (250), 10.4% suffered from subclinical anemia. There was a significant association between frequency of donation and subclinical anemia (odds ratio [OR] =6.36, P < 0.001). There was a significant association between subclinical anemia across gender (high for females; OR = 6.76, P < 0.001). There was a significant correlation between the frequency of donation and serum ferritin (Spearman correlation coefficient: −0.299), but there was no correlation observed between the frequency of donation and Hb levels. Conclusion: The study demonstrates the depletion of iron store with increasing donation frequency. This calls for continual supervision of body iron stores rather than Hb alone to ensure the continuous supply of healthy blood donors.

The pharmacokinetics of single oral dose extended-release topiramate and adverse effects after multi-dose administration in healthy cats.

Current treatment options for feline epilepsy are limited to medications that require administration of multiple doses per day or administration of a capsule or large tablet. Expanding the current treatment options could improve patient and owner compliance and optimize seizure control. Topiramate has been used sparingly in veterinary medicine, and limited pharmacokinetic studies have focused on immediate release formulations in dogs. If effective and safe, topiramate extended-release (XR) could broaden the current treatment options for feline epilepsy. The aims of this two-phase study were to establish single-dose pharmacokinetics for topiramate XR in cats, identify a dosing regimen that maintains steady-state plasma drug concentrations within a reference range extrapolated from human medicine (5-20 μg/mL), and evaluate the safety of topiramate XR in cats following multidose administration. Topiramate XR administered orally at 10mg/kg once daily for 30 days was sufficient to achieve the desired concentrations in all cats. While no clinically apparent adverse effects were observed, four out of eight cats developed subclinical anemia, calling into question the safety of topiramate XR with chronic administration. Further studies are necessary to better understand the potential adverse effects and overall efficacy of topiramate XR for the treatment of feline epilepsy.

Personalized medicine comes to a blood center near you

Personalized medicine comes to a blood center near you

Regular donor characteristics, inter-donation interval and the presence of subclinical anemia – A 3-year observational single-center study

Regular donor characteristics, inter-donation interval and the presence of subclinical anemia – A 3-year observational single-center study

Long-Term Clonal Inversion in an MDS-RS Case with Dual SF3B1 Mutations

Recent large-scale studies have traced SF3B1 mutations as a driving event in clonal establishment and expansion, and a hallmark of myelodysplastic syndrome with ring sideroblasts (MDS-RS). However, the mechanisms underlying the fitness advantage allowing SF3B1-mutant (SF3B1mt) clones to thrive remain poorly understood. Thus, tracking these events in conditions of low noise is crucial to our comprehension of clonal hematopoiesis. Here we report a 12-year clinical and molecular follow-up of a unique dual SF3B1mt MDS-RS case displaying a dynamic state of clonal competition between two clones propagated by a N626D and K666N mutation, respectively (Panel A). After an initial rapid expansion of the N626D clone compared to the relatively stable K666N clone during the initial follow-up period of ~2 years, the K666N clone spontaneously expanded at expense of the N626D clone to eventually dominate the bone marrow, driving a complete inversion of clonal prevalence. Clinically, these active shifts of high clonal involvement in the bone marrow were accompanied by stable subclinical anemia (median 12.5 g/L, range 12.0 - 13.2 g/L) and a continued decrease in the ring sideroblast phenotype over time (from 42% to 8% RS) in the absence of any treatment. The stability of this patient's clinical profile was therefore considered as unlikely to confound further characterization. Through a combination of whole-genome sequencing (WGS) of hematopoietic stem and progenitor cell (HSPC)-generated colony-forming units (CFU), combined DNA + RNAseq (TargetSeq) of FACS-purified hematopoietic stem cells (HSCs) and megakaryocyte-erythroid progenitor cells (MEP), and high-throughput 3'-based 10X Genomics single-cell RNAseq of CD34+ HSPCs, we molecularly characterized the two distinct SF3B1mt clones in bone marrow samples acquired before, during and after the points of clonal inversion (Panel B). Using WGS of single cell-derived colonies, we established that the acquisition of either the N626D or K666N mutation had preceded the diagnosis of MDS-RS by at least 20 years. Moreover, both mutations were associated with an increased mutational rate as compared to wildtype colonies, and the two clones presented distinct patterns of additional coding mutations as potential co-drivers of expansion. Mirroring previous characterizations of SF3B1mt HSPCs, we identified a common and deleterious alternative splicing profile to both genotypes via TargetSeq which included mis-splicing events in the known SF3B1mt targets MAP3K7 and SEPTIN6. In addition, we identified mutation-specific splicing profiles as potentially responsible for distinct downstream distinctions between both clones. Through this analysis, we identified the K666N-specific loss of expression of the tumor suppressors HOXA5, RGCC and NEURL1 as potential compound factors to the known higher risk underlying SF3B1K666N mutations. Finally, we disentangled clone-driven and aging-driven transcriptomic changes to identify a significant decrease of the early hematopoietic controllers ID1, ID2 and ID3 as a potential mechanism of aging-related cellular senescence. In conclusion, this case study comprises a unique long-term follow-up of the clonal dynamics underlying two co-existing, distinct and competing SF3B1mt clones which identifies subtle molecular changes and differences underlying the expansion and progression of SF3B1mt clones. *Moura PL, Hofman IJF, Nannya Y and Aliouat A contributed equally to this work. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparative analysis of hematological parameters of first-time and repeat blood donors: Experience of a blood bank in southern Nigeria

IntroductionThe safety of a blood transfusion practice is anchored on safe blood from a healthy donor, while further protecting the donor from future harm. This study aimed to evaluate the hematological parameters of blood donors in view of their donor category to aid in assessing the safety threshold in terms of donation frequency. MethodsThis study made use of the descriptive cross-sectional design. The blood donors were bled and their samples analyzed using a hematology autoanalyzer. ResultsA total of 178 male blood donors were recruited. Most of the donors were aged 18 to 39 years and were mostly students. A greater part of them were repeat donors who had donated blood more than four times. First- and second-time donors constituted the majority of the voluntary donors. While the total red cell count was significantly lower in repeat third-time donors, the hemoglobin and hematocrit of the first-time donors were significantly higher than those of the repeat fourth-time donors. The mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) of the first-time donors were significantly higher than those of the repeat fifth-time donors. The red cell distribution width (RDW) and mean platelet volume (MPV) were significantly lower in the first-time donors from those of the sixth- and seventh-time donors, respectively. Most of the fifth-time donors have subclinical anemia. There was more subclinical anemia in commercial donors than in voluntary donors. ConclusionRepeat donors more than fifth-time donors are at risk of donation-induced iron deficiency anemia.

Detection of Anti-Erythrocyte Antibodies in Dogs with Inflammatory Bowel Disease (IBD).

Simple SummaryIn human patients with intestinal inflammation, many other diseases may occur due to it, but their presence in dogs is rarely described. The aim of the study was to prove if antibodies against red blood cells (RBC) were present in dogs with chronic intestinal inflammation (IBD), as it is demonstrated for humans, and to described other RBC abnormalities. IBD was diagnosed using the current consensus and a disease severity score was assessed for each dog, as well as score from endoscopy and intestinal histology. Our results showed that most of dogs had antibodies against RBC and 50% of dogs showed RBC regeneration in addition to chronic inflammation hematologic findings. In IBD dogs, the presence of anti-RBC antibodies and the other RBC alterations may suggest a subclinical RBC damaged (hemolysis).Several extra-intestinal manifestations, including immune-mediated cytopenias, are reported in human inflammatory bowel disease (IBD), whereas they are poorly documented in dogs. Hypothesizing that immune-mediated subclinical anemia can occur in canine IBD, the study aim was to evaluate the erythrogram and the presence of anti-RBC antibodies in dogs with IBD. IBD was diagnosed according to the following criteria: chronic gastrointestinal signs, ruling out of extra-intestinal diseases, no improvement with diet trial, histological evidence of inflammatory infiltration, and improvement after immunosuppressant therapy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) endoscopic and histopathological scores were assessed for each dog. Twenty-five dogs were enrolled, and each dog had a CBC evaluation prior to endoscopy. The CBC was performed using laser hematology analyzer and blood smears were carefully reviewed for the presence of nucleated RBC, anisocytosis, polychromasia, and Howell–Jolly bodies. IgG and IgM anti-RBC antibodies were evaluated with flow cytometry. A high frequency of positive cases for anti-RBC antibodies in dogs with IBD (17/25 dogs) was ascertained. Approximatively 50% of dogs showed some hematologic features of RBC regeneration in addition to hematologic findings consistent with chronic inflammation. Anti-RBC antibodies and signs of erythroid regeneration may suggest possible subclinical chronic immune-mediated hemolysis that can cause anemia in dogs with IBD, together with the chronic inflammation.

Higher Hepcidin Levels in Adolescents with Obesity Are Associated with Metabolic Syndrome Dyslipidemia and Visceral Fat.

Tightly regulated iron metabolism prevents oxidative stress. Hepcidin is a hormone that regulates iron flow in plasma; its production is induced by an iron overload and by inflammation. It inhibits iron entry into the circulation by blocking dietary absorption in the duodenum, the release of recycled iron from macrophages and the exit of stored iron from hepatocytes. Varied signals responding to iron stores, erythropoietic activity and host defense converge to regulate hepcidin production and thereby affect iron homeostasis. Although it is known that hepcidin increases when interleukin 6 (IL-6) increases, the relationship between hepcidin, dyslipidemia, insulin resistance (IR) and visceral adiposity index (VAI) in adolescents with obesity is unclear. In this cross-sectional study of 29 obese adolescents and 30 control subjects, we explored the difference of hepcidin, iron metabolism markers and IL-6 between obese and non-obese adolescents, and identified associations with inflammation, atherogenic dyslipidemia and IR. As compared to lean controls, obese participants showed 67% higher hepcidin: 14,070.8 ± 7213.5 vs. 8419.1 ± 4826.1 pg/mLc; 70% higher ferritin: 94.4 ± 82.4 vs. 55.1 ± 39.6 pg/mLa and 120% higher IL-6: 2.0 (1.1–4.9) vs. 0.9 (0.5–1.3) pg/mLd. Transferrin, soluble transferrin receptor and total body iron (as measured by sTFR/ferritin, log10 sTFR/ferritin ratio and sTFR/log ferritin ratios) were not different between the two cohorts. In the whole cohort, hepcidin correlated with VAI (r = 0.29a), sd-LDL (r = 0.31b), HOMA-IR (r = 0.29a) and IL-6 (r = 0.35c). In obese adolescents hepcidin correlated with TG (r = 0.47b), VLDL-C (r = 0.43b) and smaller LDL2 (r = 0.39a). Hepcidin elevation in adolescents with obesity is linked more to inflammation and metabolic alterations than to iron metabolism since the other markers of iron metabolism were not different between groups, except for ferritin. Studies addressing the long-term effects of higher hepcidin levels and their impact on subclinical anemia and iron status are warranted. a p < 0.05; b p < 0.01, c p < 0.001 d p < 0.0001.

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

IntroductionIron profiles in patients with type 2 diabetes (T2D) are inconsistent. In this study, we assessed the levels of hepcidin, a regulatory protein involved in iron homoeostasis, in patients with T2D. We further evaluated the surrogate markers of hepcidin action, particularly those associated with erythropoiesis. MethodsThis systematic review and meta-analysis was reported following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched for relevant studies in electronic databases from inception until 31 October 2020 without any language restriction. The random effects model was used to calculate effect estimates, and outcomes were reported as either standardised mean difference (SMD) or mean differences (MD), 95 percent confidence interval (95% CI). ResultsEleven studies involving 2 620 participants were included in this study. Patients with T2D had a slight increase in hepcidin levels when compared to controls SMD: 0.07 [95% CI: -0.30, 0.44]. The subgroup analysis showed that studies involving patients with T2D who were overweight reported elevated hepcidin levels SMD: 0.35 [95% CI: 0.07, 0.62] whilst those with grade I obesity described reduced levels SMD: -0.42 [95% CI: -1.21, 0.38]. All T2D patients had low levels of haemoglobin MD: -0.23 g/dl [95% CI: -0.46, -0.01] irrespective of body weight. ConclusionThe levels of hepcidin are altered in patients with T2D and are disproportionately influenced by weight. Moreover, patients with T2D present with subclinical anaemia despite elevated iron stores. The regulation of hepcidin in patients with T2D is dependent on several factors and vary greatly, thus its sole use in clinical settings may be less beneficial.

Fatigability as a Predictor of Subclinical and Clinical Anemia in Well-Functioning Older Adults.

Anemia is a common condition in older adults for which fatigue, the primary symptom, often goes unrecognized as individuals typically equilibrate their activity to avoid fatigue. Whether assessing fatigability (i.e., susceptibility to fatigue) facilitates identification of anemia is unknown. This study examines the association between fatigability and prevalent, incident, and persistent subclinical and clinical anemia in well-functioning older adults. Longitudinal analysis of 905 well-functioning men and women aged 60 to 89 years and followed for 1 to 5 years from the Baltimore Longitudinal Study of Aging conducted at the National Institute on Aging, Clinical Research Unit, Baltimore, MD. Perceived fatigability was assessed as a rating of perceived exertion (RPE) from 6 to 20 following a 5-minute treadmill walk at 1.5 mph (.67 m/s); fatigue was assessed as reported unusual tiredness in the past month. Clinical anemia was defined using World Health Organization hemoglobin cutpoints of below 13 g/dL and below 12 g/dL for men and women, respectively, and subclinical anemia was defined as 13.0 to 13.9 g/dL and 12.0 to 12.9 g/dL, respectively. Overall, 14% of participants had clinical and 30% had subclinical anemia at baseline. Each increment (1 RPE) of fatigability was associated after covariate adjustment with 14% (95% confidence interval [CI] = 5-25%, P = .005) and 8% (CI = 1-17%; P = .031), respectively, greater likelihood of prevalent clinical and subclinical anemia. An average of 2.2 years later, each 1 RPE increment in baseline fatigability predicted an 11% (CI = 2-20%; P = .016) higher likelihood of incident and/or persistent subclinical and clinical anemia. Reports of unusual tiredness were associated with prevalent subclinical anemia only. This study provides evidence that perceived fatigability may help identify well-functioning older adults with borderline to clinical anemia who are on a trajectory of persistently suboptimal or worsening hemoglobin status. Assessing fatigability may facilitate earlier diagnosis of health conditions that underlie persistent suboptimal hemoglobin status. J Am Geriatr Soc 68:2297-2302, 2020.

Multiple nutritional currencies shape pregnancy in a large herbivore

Nutritional condition embodies environmental conditions experienced by animals with survival and reproductive consequences. Body fat is often associated with ungulate fecundity; however, other nutritional currencies may limit fecundity. Using data from 129 moose (Alces alces (Linnaeus, 1758)) monitored over 429 moose-years, we examined the limiting role of multiple nutritional currencies on pregnancy rates while concurrently assessing the influence of age and prior reproduction. Females tended to be pregnant in successive years, suggesting differences in individual or habitat quality. However, probability of pregnancy declined with survival of calves from prior litters, indicating a reproductive cost to rearing offspring. Pregnancy was positively associated with serum iron (Fe), body fat, body mass, and serum protein. The best model predicting pregnancy included serum Fe, body fat, and age class, with serum Fe being the strongest single predictor. Moose with Fe concentrations considered deficient in cattle (Bos taurus Linnaeus, 1758) had pregnancy rates of 33%–35%, whereas 89%–91% of individuals with sufficient Fe were pregnant. We subsequently evaluated hypotheses concerning factors potentially limiting Fe concentrations, including Fe-deficient diet, chronic infection, parasitism, and malnutrition. The best supported hypothesis was energy and protein malnutrition constrained Fe stores. We conclude that subclinical anemia due to nutritional constraints can limit or indicate limits in moose fecundity.

Evaluation of Subclinical Anaemia Using Serum Ferritin Level in Rural Antenatal Mothers

Prevalence of anaemia in all the groups of women is higher in India as compared to other developing countries [1] ; leading to maternal mortality, increase in Neonatal Intensive Care Unit (NICU) admission and under nutrition in childhood and adolescence. The aim of this study is to assess serum ferritin levels in non-anaemic (according to Haemoglobin concentration) mothers with Haemoglobin > 10g/dl and to express that Haemoglobin concentration of blood is inadequate to diagnose subclinical iron deficiency anaemia in rural antenatal mothers. Blood samples were collected from 200 antenatal women visiting Government Sivaganga Medical College and Hospital, Sivaganga, Tamil Nadu, India. Among them 56.5 % (n=113) prenatal women were in the 3 rd Trimester of pregnancy, 30 % (n=60) in the second Trimester and 13.5 % (n=27) in the first Trimester. Their mean age was 24.5 years, mean height was 153.9 cm. During clinical examination 9 women (4.5 %) were found to be clinically anaemic and the remaining 191 samples were classified according the range of Haemoglobin level. Of the 191 samples 48 samples (24%) containing Hb ≥ 10 g/dl (non anaemic) were taken for study of serum ferritin. The mean level of Ferritin decreases from first trimester to second to third trimester in the decreasing order of 40.8ng/ml, 36.4ng/ml and 27.6 ng/ml respectively. There is a positive correlation between Haemoglobin and Serum Ferritin in three different trimesters of antenatal women. On assessing Haemoglobin alone 76% of antenatal women under study were found to be anaemic. In non-anaemic women 16.7 % were found to be anaemic (iron deficiency anaemia) based on Serum ferritin level (less than 12 ng/ml). Totally 80% of antenatal women are found to be anaemic in this study area. Thus an increase of 4% detection rate and early diagnosis of

Maternal Iron Deficiency Heightens Fetal Susceptibility to Metabolic Syndrome in Adulthood

Iron is involved in the functional conformation of hemoglobin; it facilitates hemoglobin binding to oxygen. Iron also has a critical role in erythropoiesis. When erythroblasts proliferate and differentiate, they require large amounts of iron for hemoglobin synthesis. The heme moiety of erythroblasts requires iron for synthesis, and it regulates globin production. Thus, iron deficiency (ID) causes anemia, which is associated with many diseases. Because ID in the adult has a detrimental influence on erythrocyte function, maternal ID affects fetal development; thereafter, many physiological functions may be altered in the offspring. In rats fed a low-iron diet, although maternal ID did not cause severe anemia in the dam, brain development in the offspring was profoundly impaired; their offspring showed an increased auditory brainstem response time later in life, which suggested an impairment in brain development (1). Thus, subclinical anemia in the mother during early pregnancy may be a risk factor for abnormal central nervous system development in the fetus. The authors also showed that there was a time window for the susceptibility of brain development to ID (1). The fetal stage was thought to be the most vulnerable stage during development (2). The bottom line was that, when a fetus had experienced maternal ID, health problems become manifest in adulthood, despite adequate adult nutrition. Although animals are resistant to diet-induced obesity under normal circumstances, feeding with a high-fat diet (HFD) induces obesity in many experimental animals. Therefore, HFD is widely used as a model for the Western diet, which is thought to be an important risk factor for obesity. In turn, obesity increases the risk for metabolic syndrome, which includes cardiovascular disease. Therefore, the relationship between obesity and the Western diet has a profound impact on public health. Because the time range of highest vulnerability in brain development occurs in the fetal stage, one might expect that some abnormal development of the brain at that time could affect the adult’s susceptibility to obesity (3). In fact, the thrifty phenotype hypothesis proposed that poor nutrition in early life causes subsequent development of the metabolic syndrome in adults (4). It is now recognized that intrauterine undernutrition or excessive maternal feeding, including a HFD, affects the developmental programming of the offspring, and changes can be manifest in adulthood (5). Thus, the risk for adult health problems, particularly metabolic syndrome, can be markedly influenced by fetal and prenatal environmental exposures. Interestingly, many abnormal feeding behaviors are manifest only with the HFD. For example, heterozygote carriers of the proopiomelanocortin gene mutation are predisposed to obesity. Under normal feeding conditions, these mice maintained a normal weight; however, when fed a HFD, these mice became significantly obese (6). This also occurred with pharmacological receptor manipulations (7). Similar responses were observed in neuropeptide Y knockout mice. When fed normal chow, they look healthy, but when fed a HFD, they become obese (8). These are only a few examples, but they showed that the HFD is useful for revealing diseases. In this issue of Endocrinology, Bourque et al. (9) reported that mouse offspring exposed to maternal ID during the gestational period developed a susceptibility to HFD-induced obesity; in addition, they developed glucose intolerance and increases in blood pressure. These symptoms are indicative of metabolic syndrome. Dams fed a

Haematological and serum biochemical reference values for apparently healthy working horses in Pakistan

This study aimed to establish comprehensive reference values for horses working in developing countries, and to compare them against accepted values for horses in developed countries, supporting diagnosis and clinical decision-making. Horses in developing countries usually perform strenuous work in hot, resource-limited conditions, so their ‘normal’ blood parameters may differ from other horses. Blood was analysed from 203 working horses in Pakistan, meeting defined clinical criteria. Age, sex, body condition and work-type showed small significant effects, but none were clinically relevant. Of the 32 reference intervals, 28 overlapped those of UK horses. However, the entire reference interval for creatine kinase was higher than for UK horses, while those for erythrocytes, albumin and albumin:globulin ratio were lower. Haematocrit and haemoglobin concentrations were also low. Therefore, apparently healthy working horses may have chronic muscle damage from overwork, and may have sub-clinical anaemia. Interventions combating these conditions could improve animal welfare, although it is unclear whether differences between UK and Pakistan reference values reflect chronic abnormalities, or are in fact physiological adaptations enabling horses to cope with the challenging conditions.

Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study.

To determine specific physiological correlates of the geriatric syndrome of frailty that warrant further investigation. Population-based case-control study. General Clinical Research Center at Johns Hopkins Bayview Medical Center. Community-dwelling adults aged 74 and older from Baltimore, Maryland. Frailty status was determined using a recently validated screening tool that consists of weight loss, fatigue, low levels of physical activity, and measurements of grip strength and walking speed. Serum interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay, and standard complete blood count was performed using a Coulter counter. Eleven frail and 19 nonfrail subjects with mean age +/- standard deviation of 84.9 +/- 6.7 vs 81.3 +/- 4.1 years, respectively, completed the study. The frail subjects had significantly higher serum IL-6 levels and significantly lower hemoglobin and hematocrit than the nonfrail subjects (4.4 +/-2.9 vs 2.8 +/- 1.6 pg/mL, 12.1 +/- 1.1 vs 13.9 +/- 1.0 g/dL, and 35.8% +/- 3.1% vs 40.6% +/- 2.8%, respectively). No significant difference was observed in mean corpuscular volume, red blood cell distribution width, or white blood cell and platelet counts between the frail and nonfrail groups. Furthermore, there was an inverse correlation between serum IL-6 level and hemoglobin (Pearson's correlation coefficient: -0.46) and hematocrit (-0.48) in the frail group but not in the nonfrail group. These results suggest that frail subjects have evidence of inflammation and lower hemoglobin and hematocrit levels. This subclinical anemia is normocytic and is hence unlikely due to myelosuppression or iron deficiency and is potentially related to the increased chronic inflammatory state marked by serum IL-6 elevation. Further studies are indicated to better characterize the immune and hematological changes that underlie frailty.

Subclinical anaemia of chronic disease in adult patients with cystic fibrosis

Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute ‘relative anaemia’. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers ( n=17) and in adult patients with cystic fibrosis ( n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers ( P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation ( P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron ( P=0.002), transferrin ( P=0.02), and total iron-binding capacity ( P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.

Soluble transferrin receptors in anaemia of pregnancy

Anaemia is one of the most common disorders in pregnancy. The most common cause is iron deficiency. Iron deficiency anaemia is relatively easy to diagnose using a serum ferritin of <15 ng/ml. However, because ferritin is an acute phase reactant, the diagnosis of iron deficiency anaemia in hospitalised or ill patients may be difficult, since serum ferritin may be normal or raised, even in the face of iron deficiency. Soluble transferrin receptor assay (STfR) may be useful in these situations because it reflects the degree of iron requirement in relation to supply, and it is not an acute phase reactant. This study was undertaken to detect subclinical anaemia in pregnant women and to correlate STfR assay with the current diagnostic tests for iron deficiency anaemia. One hundred and fifty-three consenting pregnant women seen at the antenatal clinic at King Edward VIII Hospital (KEH) were recruited. Women on haemantinics, who had renal failure, haemoglinopathy and blood transfusion in the past 3 months, were excluded. An ELISA technique was used for the assay of STfR while standard methodology was used for the other biochemical and haematological assays (FBC, urea, creatinine, c reactive protein and iron studies). One hundred and fifty subjects were included in the final analysis. Seventy-two (48%) had varying degrees of iron deficiency anaemia. In 70% (105) of the samples analysed, serum ferritin and STfR agreed on the presence/absence of iron deficiency anaemia. STfR and S:F were 75% and 86% sensitive; 63% and 82% specific, respectively. The calculated positive and negative predictive values are: STfR 64% and 75%; S:F 84% and 87%; Hb 58% and 57%; mean corpuscular volume 91% and 55%, respectively. Ferritin remains the gold standard for the diagnosis of iron deficiency anaemia. However, because ferritin is an acute phase reactant, soluble transferrin receptor assay may be a better test in ill and hospitalised patients where ferritin may be normal or elevated, despite iron deficiency.

Immune response against toxoplasma and sarcoscystis infections in ruminants : diagnosis and prospects for vaccination

Toxoplasma gondii and a variety of Sarcocystis species are common cyst-forming coccidian parasites of domestic ruminants worldwide. T. gondii infection is a major cause of ovine and caprine abortion and perinatal mortality, but does not appear commonly to cause significant disease in other ruminants. Sarcocystis infections are probably most important in growing ruminants in which they can cause subclinical anaemia and reduced weight gain. The life cycles, pathogenesis and current knowledge of immunity to these protozoa, in ruminants, are reviewed. Although clinical signs may suggest a diagnosis, confirmation requires the use of specific immunological methods such as serology and immunohistochemistry. These are discussed and the necessity for using characterised antigens and antisera is emphasised. Whereas live Toxoplasma "vaccines" may be effective in sheep and goats, the eventual preparation of a killed vaccine capable of inducing long-term protection is of the utmost importance. To achieve this goal it will be necessary to identify the specific antigens capable of stimulating protective immunity and to conduct further research on both the pathogenesis of toxoplasmosis and fundamental aspects of the immune response of pregnant ruminants to T. gondii.

The value of whole cottonseed in a wheat-based maintenance ration for sheep

The effects of fuzzy whole cottonseed (WCS) on the performance and health of sheep were examined. Thirty 2-year-old Merino wethers were divided into 3 equal groups and offered maintenance rations for 138 days, with whole wheat grain to WCS ratios of 100:O (diet A), 75:25 (B) and 50:50 (C). Liveweight changes for diets A, B and C were -0.3, +4.4 and +3.0 kg respectively, and were significantly (P&lt;0.05) greater on WCS diets. Wool growth rates were also significantly (P&lt; 0.01) improved by the addition of WCS, with treatment means being 0.65 (diet A), 0.82 (B) and 0.88 mg/cm2.day (C). Digestibility of DM in diet C (677 g/kg) was significantly (P&lt; 0.001) lower than in diets A (782) and B (777 g/kg), perhaps because of increased fibre and oil in the ration. Subclinical anaemia and muscle damage were evident in animals given WCS by days 43 and 127 respectively. Post mortems and histological examination revealed renal haemosiderosis in sheep given WCS, with increased severity at 50% inclusion in the ration. Despite the reduction in digestibility and the subclinical effects on health, at least 25% WCS can be safely included in a wheat-based maintenance ration for wethers and this ration has production advantages over wheat alone. Caution is advised in feeding higher levels of WCS or feeding such a ration for more than 5 months.

Studies on a family with Hb J Calabria (alpha 2 beta 2 64 (E8) Gly replaced by Asp).

Hb J Calabria is a fast moving hemoglobin variant which was found in an Italian family by Vecchio et al (1), and in a French family by Blouquit et al. who studied its functional properties (2). The original family described by Vecchio et al. in which both Hb J Calabria and beta-thalassemia were present has been reexamined and is the subject of the present study. Hematological and clinical features of the carriers are described. The heterozygous carriers of Hb J Calabria showed only mild variable subclinical anemia and levels of the abnormal hemoglobin ranging from about 33 to 42%. The Hb J Calabria/beta-thalassemia double heterozygote showed a moderate chronic hemolytic anemia with alterations of the RBC indices and morphology in addition to splenomegaly. The relationship between structural abnormality, functional properties and clinical expression of Hb J Calabria is discussed.